{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T07:32:14Z","timestamp":1793345534893,"version":"4.5.0"},"reference-count":48,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T00:00:00Z","timestamp":1787184000000},"content-version":"vor","delay-in-days":19,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Sleep deprivation (SD) is common but underrecognized in intensive care unit (ICU) patients and contributes to delirium and long\u2010term neurocognitive deficits. Propofol is widely used for titratable ICU sedation and has potential neuroprotective effects, but the mechanisms underlying its cognitive benefits during recovery sleep remain unclear. Evidence shows that coupling between slow oscillations (SO) and spindles during sleep is associated with memory consolidation processes. We hypothesized that propofol\u2010facilitated recovery sleep after acute SD would strengthen SO\u2013spindle coupling aligned to the SO up state and thereby improve cognition.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Male Sprague\u2013Dawley rats (8\u201312\u2009weeks, total\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200967) were assigned to control (CON), SD without intervention (SDN), spontaneous recovery (SDS), or propofol\u2010supported recovery (SDP). All SD groups underwent 48\u2009h of total deprivation. During recovery, SDP received propofol (20\u2009mg\u00b7kg\n                      <jats:sup>\u22121<\/jats:sup>\n                      \u00b7h\n                      <jats:sup>\u22121<\/jats:sup>\n                      , 6\u2009h), whereas SDS recovered naturally. Spatial learning and memory were tested by the Barnes maze (BM); recognition memory by 2\u2010h and 24\u2010h novel object recognition (NOR) for short\u2010 and long\u2010term recognition memory. Sleep electroencephalography (EEG) and electromyography (EMG) were recorded for 12\u2009h during recovery in SDS and SDP. We quantified SO and spindle parameters and SO\u2013spindle phase coupling. Separate animals were analyzed for cortical Na\n                      <jats:sup>+<\/jats:sup>\n                      \u2010K\n                      <jats:sup>+<\/jats:sup>\n                      \u20102Cl\n                      <jats:sup>\u2212<\/jats:sup>\n                      cotransporter 1 (NKCC1)\/K\n                      <jats:sup>+<\/jats:sup>\n                      \u2010Cl\n                      <jats:sup>\u2212<\/jats:sup>\n                      cotransporter 2 (KCC2) expression ratio.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Sleep deprivation impaired BM and NOR performance. Propofol during recovery restored spatial performance and 24\u2010h recognition retention. Propofol also increased SO density compared with SDS (11.13\u2009\u00b1\u20090.14 vs. 9.49\u2009\u00b1\u20091.26 events\/min,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.040) and improved phase\u2010accurate SO\u2013spindle alignment, with higher phase\u2010vector projection (Vproj; 0.30\u2009\u00b1\u20090.11 vs. \u22120.33\u2009\u00b1\u20090.37,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.036), increased up\u2010phase events (0.38\u2009\u00b1\u20090.01 vs. 0.16\u2009\u00b1\u20090.10,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.036), and significant up\u2010state preference only in SDP (\n                      <jats:italic>V<\/jats:italic>\n                      \u2010test,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.035). Molecularly, propofol decreased the NKCC1\/KCC2 ratio by reducing NKCC1 and increasing KCC2.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Propofol\u2010facilitated recovery sleep supports spatial and recognition memory, accompanied by up\u2010state\u2010precise SO\u2013spindle coupling and reduced NKCC1\/KCC2. These findings suggest SO\u2013spindle alignment may serve as a candidate EEG marker of recovery sleep and highlight chloride\u2010transport\u2010related pathways as therapeutic targets for SD\u2010related cognitive impairment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns.71076","type":"journal-article","created":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T04:47:32Z","timestamp":1787287652000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Propofol\u2010Facilitated Recovery Sleep Modulates Cognitive Function via Slow Oscillation\u2010Spindle Coupling After Acute Sleep Deprivation in Rats"],"prefix":"10.1002","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7299-3668","authenticated-orcid":false,"given":"Chenyi","family":"Yang","sequence":"first","affiliation":[{"name":"Nankai University  Tianjin China"},{"name":"Department of Anesthesiology Central Hospital, Tianjin University (Formerly Tianjin Third Central Hospital)  Tianjin China"},{"name":"Tianjin University  Tianjin China"},{"name":"Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Central Hospital, Tianjin University (Formerly Tianjin Third Central Hospital)  Tianjin China"},{"name":"Tianjin University  Tianjin China"},{"name":"Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases  Tianjin China"},{"name":"The Third Central Clinical College of Tianjin Medical University  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyi","family":"Wang","sequence":"additional","affiliation":[{"name":"Nankai University  Tianjin China"},{"name":"Department of Anesthesiology Central Hospital, Tianjin University (Formerly Tianjin Third Central Hospital)  Tianjin China"},{"name":"Tianjin University  Tianjin China"},{"name":"Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Central Hospital, Tianjin University (Formerly Tianjin Third Central Hospital)  Tianjin China"},{"name":"Tianjin University  Tianjin China"},{"name":"Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases  Tianjin China"},{"name":"The Third Central Clinical College of Tianjin Medical University  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0084-2342","authenticated-orcid":false,"given":"Haiyun","family":"Wang","sequence":"additional","affiliation":[{"name":"Nankai University  Tianjin China"},{"name":"Department of Anesthesiology Central Hospital, Tianjin University (Formerly Tianjin Third Central Hospital)  Tianjin China"},{"name":"Tianjin University  Tianjin China"},{"name":"Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases  Tianjin China"},{"name":"The Third Central Clinical College of Tianjin Medical University  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,20]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.202301\u20100184ST"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13054\u2010024\u201005118\u20104"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.iccn.2022.103349"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13054\u2010024\u201005161\u20101"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/ccm.0000000000003299"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2023.1199685"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.iccn.2025.104138"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1301372"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13054\u2010022\u201004077\u2010y"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13613\u2010025\u201001429\u2010z"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2023.1140275"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1221180110"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/aln.0000000000000436"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2017.04.011"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/cns.14798"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1523\/jneurosci.13\u201008\u201003252.1993"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1523\/jneurosci.1318\u201004.2004"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1523\/jneurosci.22\u201024\u201010941.2002"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2017.11.020"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010018\u201036557\u2010z"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1523\/jneurosci.2193\u201023.2024"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010020\u201058496\u20104"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nlm.2019.107100"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchemneu.2020.101850"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.14418"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0224642"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0031\u20109384(97)00460\u20105"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/sleep\/zsae061"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/ejn.14906"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00014.2006"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010018\u20100716\u20108"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00042.2018"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1851"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1037\/a0018883"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2017.07.010"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102869.2010.00895.x"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1097\/ccm.0000000000006574"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000539\u2010199803000\u201000040"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10571\u2010017\u20100530\u20100"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.smrv.2005.05.002"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593\u2010019\u20100467\u20103"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593\u2010023\u201001381\u2010w"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/16697"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn920"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2013.11.004"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/79848"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2003.08.051"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2372"}],"container-title":["CNS Neuroscience &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cns.71076","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cns.71076","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cns.71076","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T06:53:01Z","timestamp":1793343181000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cns.71076"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8]]},"references-count":48,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["10.1002\/cns.71076"],"URL":"https:\/\/doi.org\/10.1002\/cns.71076","archive":["Portico"],"relation":{},"ISSN":["1755-5930","1755-5949"],"issn-type":[{"value":"1755-5930","type":"print"},{"value":"1755-5949","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8]]},"assertion":[{"value":"2025-12-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-28","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e71076"}}